The standard of care for patients with superficial bladder cancer is transurethral resection of the bladde or followed by six weeks of intravesical BCG. This approach not only increases the surgical cure rate but also prolongs the time to recurrence in failures. The mechanism of this anti-tumor effect is widely felt to be immunologic. However, there is no evidence for a tumor-specific response and thus it is a consensus that tumo deposits are eradicated as a bystander effect of the inflammation associated with the BCG-cystitis. To initiate a tumor-specific immune response, we propose to utilize vaccinia virus recombinants to introduce immune active cytokines into the tumor with a resultant recruitment of antigen presenting cells and expression of pro-immune cytokines. As a necessary step in the development of recombinant vaccinia strategies for the therapy of bladder cancer, we plan to conduct a Phase I/Il study of intravesical vaccinia virus in patients with BCG refractory superficial bladder cancer which will address four key issues: i) the safety of intravesical vaccinia; 2) the ability to sus vaccrnia gene fimction in the bladder over the course of therapy; 3) the immunologic effects of the vaccinia vecto itself; and 4) the "baseline" of antitumor activity induced by the wild type viral vector. These studies will provide critical data for subsequent use of vaccinia recombinants.